Macromolecular assemblies play an important role in all cellular processes. While there has recently been significant progress in protein structure prediction based on deep learning, large protein complexes cannot be predicted with these approaches. The integrative structure modeling approach characterizes multi-subunit complexes by computational integration of data from fast and accessible experimental techniques. Crosslinking mass spectrometry is one such technique that provides spatial information about the proximity of crosslinked residues. One of the challenges in interpreting crosslinking datasets is designing a scoring function that, given a structure, can quantify how well it fits the data. Most approaches set an upper bound on the distance between Cα atoms of crosslinked residues and calculate a fraction of satisfied crosslinks. However, the distance spanned by the crosslinker greatly depends on the neighborhood of the crosslinked residues. Here, we design a deep learning model for predicting the optimal distance range for a crosslinked residue pair based on the structures of their neighborhoods. We find that our model can predict the distance range with the area under the receiver-operator curve of 0.86 and 0.7 for intra- and inter-protein crosslinks, respectively. Our deep scoring function can be used in a range of structure modeling applications.
Bibliographical noteFunding Information:
D.S. and S.C. are supported by the Israeli Science Foundation (ISF 1466/18). Molecular graphics and analyses performed with UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01‐GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases.
© 2023 The Authors. Proteomics published by Wiley-VCH GmbH.
- crosslinking mass spectrometry
- deep learning
- protein structure
- protein–protein interactions